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Poisonings related to consumption of the false morel Gyromitra esculenta, a highly regarded fungus eaten mainly in Finland and by some in parts of Europe and North America, had been reported for at least a hundred years. Experts speculated the reaction was more of an allergic one specific to the consumer, or a misidentification, rather than innate toxicity of the fungus, due to the wide range in effects seen. Some would suffer severely or perish while others exhibited no symptoms after eating similar amounts of mushrooms from the same dish. Yet others would be poisoned after eating the fungus for many years without ill-effects.[1] In 1885, Böhm and Külz described helvellic acid, an oily substance they believed to be responsible for the toxicity of the fungus.[2] The identity of the toxic constituents of Gyromitra species eluded researchers until 1968, when N-methyl-N-formylhydrazone was isolated by German scientists List and Luft and named gyromitrin. Each kilogram of fresh false morel had between 1.2 and 1.6 grams of the compound.[3]

Gyromitrin is a volatilewater-solublehydrazine compound hydrolyzed in the body into monomethylhydrazine (MMH). Other N-methyl-N-formylhydrazone derivatives have been isolated in subsequent research, although they are present in smaller amounts. These other compounds would also produce monomethylhydrazine when hydrolyzed, although it remains unclear how much each contributes to the false morel's toxicity.[4]

The toxicity of gyromitrin varies greatly according to the animal species being tested. The median lethal dose (LD50) is 244 mg/kg in mice, 50–70 mg/kg in rabbits, and 30–50 mg/kg in humans.[10] The toxicity is largely due to the MMH that is created; about 35% of ingested gyromitrin is transformed to MMH.[11] Based on this conversion, the LD50 of MMH in humans has been estimated to be 1.6–4.8 mg/kg in children, and 4.8–8 mg/kg in adults.[10]

Several Gyromitra species are traditionally considered very good edibles and several steps are available to remove gyromitrin from these mushrooms and allow their consumption. For North America, the toxin has been reliably reported from the species G. esculenta, G. gigas, and G. fastigiata. Species in which gyromitrin's presence is suspected, but not proven, include G. californica, G. caroliniana, G. korfii, and G. sphaerospora, in addition to Disciotis venosa and Sarcosphaera coronaria. The possible presence of the toxin renders these species "suspected, dangerous, or not recommended" for consumption.[12]

Gyromitrin content can differ greatly in different populations of the same species. For example, G. esculenta collected from Europe is "almost uniformly toxic", compared to rarer reports of toxicity from specimens collected from the US west of the Rocky Mountains.[13] A 1985 study reported that the stems of G. esculenta contained twice as much gyromitrin than the cap, and that mushrooms collected at higher altitudes contained less of the toxin than those collected at lower altitudes.[10]

The gyromitrin content in false morels has been reported to be in the range of 40–732 milligrams of gyromitrin per kilogram of mushrooms (wet weight).[14] Gyromitrin is volatile and water soluble, and can be mostly removed from the mushrooms by cutting them to small pieces and repeatedly boiling them in copious amounts of water under good ventilation. Prolonged periods of air drying also reduces levels of the toxin.[14] In the US, there are typically between 30 and 100 cases of gyromitrin poisoning requiring medical attention. The mortality rate for cases worldwide is about 10%.[15]

The symptoms of poisoning are typically gastrointestinal and neurological.[16] Symptoms occur within 6–12 hours of consumption, although cases of more severe poisoning may present sooner—as little as 2 hours after ingestion. Initial symptoms are gastrointestinal, with sudden onset of nausea, vomiting, and watery diarrhea which may be bloodstained. Dehydration may develop if the vomiting or diarrhea is severe. Dizziness, lethargy, vertigo, tremor, ataxia, nystagmus, and headaches develop soon after;[16]fever often occurs, a distinctive feature which does not develop after poisoning by other types of mushrooms.[17] In most cases of poisoning, symptoms do not progress from these initial symptoms, and patients recover after 2–6 days of illness.[18]

Treatment is mainly supportive; gastric decontamination with activated charcoal may be beneficial if medical attention is sought within a few hours of consumption. However, symptoms often take longer than this to develop, and patients do not usually present for treatment until many hours after ingestion, thus limiting its effectiveness.[23] Patients with severe vomiting or diarrhea can be rehydrated with intravenous fluids.[18] Monitoring of biochemical parameters such as methemoglobin levels, electrolytes, liver and kidney function, urinalysis, and complete blood count is undertaken and any abnormalities are corrected. Dialysis can be used if kidney function is impaired or the kidneys are failing. Hemolysis may require a blood transfusion to replace the lost red blood cells, while methemoglobinemia is treated with intravenous methylene blue.[24]

Pyridoxine, also known as vitamin B6, can be used to counteract the inhibition by MMH on the pyridoxine-dependent step in the synthesis of the neurotransmitterGABA. Thus GABA synthesis can continue and symptoms are relieved.[25] Pyridoxine, which is only useful for the neurological symptoms and does not decrease hepatic toxicity,[8][26] is given at a dose of 25 mg/kg; this can be repeated up to a maximum total of 15 to 30 g daily if symptoms do not improve.[27]Benzodiazepines are given to control seizures; as they also modulate GABA receptors they may potentially increase the effect of pyridoxine. Additionally MMH inhibits the chemical transformation of folic acid into its active form, folinic acid, this can be treated by folinic acid given at 20–200 mg daily.[6]

Monomethylhydrazine,[28] as well as its precursors methylformylhydrazine[29][30] and gyromitrin[31] and raw Gyromitra esculenta,[32] have been shown to be carcinogenic in experimental animals.[33][34] Although Gyromitra esculenta has not been observed to cause cancer in humans,[35] it is possible there is a carcinogenic risk for people who ingest these types of mushrooms.[29] The toxins may be cumulative[36] and even small amounts may have a carcinogenic effect.[37] At least 11 different hydrazines have been isolated from Gyromitra esculenta, and it is not known if the potential carcinogens can be completely removed by parboiling.[38]